Adult Stem Cells for Therapy of Visual Disorders

描述(由申请人提供)：没有什么比用“干细胞”重建受损视网膜的可能性更能激发视障患者或治疗他们的眼科医生的想象力了。干细胞被定义为能够分化为各种细胞类型的多潜能细胞，干细胞可以从早期胚胎或成人中获得，在适当的条件下，将分化为各种组织。干细胞已经在脐带血和成人骨髓中被发现，它们代表着一个祖细胞池，可以提供维持各种组织类型的细胞，以及在受伤或应激后拯救/修复受损组织。这些成体干细胞可能在治疗视网膜血管疾病甚至遗传性视网膜变性方面有广泛的用途。虽然在缺血性视网膜病变中，使用这些细胞来靶向新生血管并有助于稳定原本脆弱的血管似乎是直观的，但最近观察到的相关神经营养效应令人惊讶，但考虑到新出现的描述局部血管网络和视网膜病变之间存在营养性“串扰”的范例，这是合理的。 他们供应的纸巾。因此，这些细胞的潜在应用不仅包括基于细胞的各种营养和静止物质的治疗输送，还包括作为缺血性视网膜病变中观察到的不稳定新生血管的稳定成分。在这项提议中，我们将应用干细胞生物学、基因治疗、蛋白质组学、大规模基因组分析和活细胞成像等新兴技术来开发基于干细胞的疗法，用于治疗视网膜血管和退行性疾病。这将通过以下步骤实现：(1)鉴定并分离从成人骨髓和脐带血中分离出的将靶向视网膜病变血管形成并在视网膜血管和退行性疾病动物模型中发挥营养挽救作用的一部分祖细胞；(2)确定实现这些营养效应的机制；(3)设计一种制备和表征功能细胞组分的方法；以及(4)进行必要的临床前药理学、毒理学和药代动力学研究，以便将这种方法应用于临床。如果成功，这些研究将为目前无法治疗的视网膜血管和退行性疾病带来一种新的治疗模式。

DESCRIPTION (provided by applicant): Nothing more dramatically captures the imagination of the visually impaired patient or the ophthalmologist treating them than the possibility of rebuilding a damaged retina with "stem cells." Defined as pluripotent cells capable of differentiating into a variety of cell types, stem cells can be derived from early embryos or adults and, under appropriate conditions, will differentiate into a variety of tissues. Stem cells have been identified in cord blood and adult bone marrow and represent a pool of progenitor cells that may serve to provide cells that maintain various tissue types as well as rescue/repair damaged tissue following injury or stress. These adult stem cells may have wide utility in the treatment of retinal vascular diseases and even inherited retinal degenerations. While the use of these cells to target neovasculature and contribute to the stabilization of otherwise friable vessels in ischemic retinopathies may seem intuitive, an associated neurotrophic effect observed recently (Otani, et al, 2004) is surprising but reasonable given newly emerging paradigms describing the existence of trophic "cross-talk" between local vascular networks and the tissues they supply. Thus, potential applications of these cells includes not only cell based therapeutic delivery of various trophic and static substances, but also as stabilizing elements in an otherwise unstable neovasculature of the type observed in ischemic retinopathies. In this proposal we will apply emerging technologies in stem cell biology, gene therapy, proteomics, large scale genomic analysis and live cell imaging to develop stem cell-based therapies for the treatment of vascular and degenerative diseases of the retina. This will be accomplished by (1) identifying and isolating a fraction of progenitor cells from adult bone marrow and cord blood that will target diseased vasculature in the retina and exert trophic rescue effects in animal models of retinal vascular and degenerative disease; (2) determining the mechanism whereby these trophic effects are achieved; (3) engineering a process for the preparation and characterization of the functional cell fraction; and (4) conducting the necessary pre-clinical pharmacological, toxicological and pharmacokinetic studies to take this approach into the clinics. If successful, these studies will lead to a novel therapeutic paradigm for currently untreatable vascular and degenerative diseases of the retina.